Cancer Therapeutics

The Cancer Therapeutics (CT) Program has a rich history of discovering and developing cancer diagnostic and therapeutic strategies. CT faculty integrate the latest advances in bioengineering, nanotechnology, drug targeting, machine learning/artificial intelligence, and informatics for cancer drug discovery in preclinical models, laying a foundation for translation to diagnostic and therapeutic clinical and community trials that benefit New Mexico. CT promotes collaboration between clinical, population, and basic scientists across translational research initiatives. And, CT catalyzes UNMCCC team building for intellectual property and commercialization, invention disclosures, patent filing, and company startups (led by UNM's technology transfer office Rainforest Innovations), and provides leadership in investigator-initiated trial (IIT) development, Program project grants, NCTN trials, and the NCORP.

The Specific Aims of the CT Program are to

1. Aim 1: discover new targets and therapeutic agents
2. Aim 2: conduct mechanistic studies to inform clinical applications, and
3. Aim 3: translate innovative science to clinical and community cancer interventions.

Aim 1: Employ cutting-edge technologies and machine learning to identify genetic vulnerabilities and develop new therapeutic agents.

To promote inter-programmatic collaborations with CMO aimed at identifying transformative treatment strategies for clinical translation, we broadened the scope of our discovery aim. Small-molecule screening efforts have been advanced through a collaborative agreement with the Sanford Burnham Prebys Medical Discovery Institute's Center for Chemical Genomics. The inclusion of structural biology and new inter-institutional discovery initiatives will enable ultra-high-throughput screening to identify and develop new small-molecule inhibitors for unique targets. This approach is complemented by the innovative application of artificial intelligence models that account for patient heterogeneity to discover and personalize new cancer regimens. Artificial intelligence-based strategies to refine and accelerate biomarker discovery will further inform the design of precision clinical trials. Finally, the launch of a fully integrated informatics system and data warehouse, Cancer Research Integrated Informatics System (CRIIS), that combines longitudinal patient data with clinical-grade genomic data will present an opportunity for collaboration with CCPS and allow us to identify interventions to reduce the cancer burden and improve outcomes in New Mexico.

Research Accomplishments and Scientific Highlights:

• Artificial intelligence
• Diagnostic cancer imaging
• Targeted therapeutics (also Aim 2 and 3)
• Discovery of GPER/ER-selective ligands and advancement to phase II/III trials (also Aims 2 and 3)

Aim 2: Conduct mechanistic studies that will advance the development of novel therapeutics and clinical interventions.

We have prioritized the collection and clinical annotation of patient specimens to support mechanistic studies and biomarker development in order to design and advance new precision therapeutics. Leveraging innovative cancer models, including humanized and autologous patient-derived xenografts, has enabled investigators to advance silicified cancer-cell-based immune strategies, studies of steroid hormone effects in the tumor microenvironment, and cutting-edge approaches to oncolytic viral cancer therapy. Multi-PI grants led by CT members, and leadership in national consortia, expand the impact of the translational studies led by UNMCCC investigators, e.g., the launch of the phase-III national clinical trial evaluating treatment for recurrent uterine cancer (Funding: NRG-GY035). To further amplify the impact of Center members' investigator-initiated trials, CT is leading the UNMCCC Translational Science Initiative (TSI) to enhance the translation of UNMCCC scientific findings to clinical and community interventions.

Research Accomplishments and Scientific Highlights:

• Nanoscience-enabled immune therapy
• Innovative cell therapy platforms for cancer prevention and treatment (also Aim 3)
• Oncolytic immunotherapy
• Targeted therapeutics (also Aim 1 and 3)
• Discovery of GPER/ER-selective ligands and advancement to phase II/III trials (also Aims 1 and 3)
• Combination immune therapy for ovarian cancer evaluated in two national trials (also Aim 3)

Aim 3: Translate UNMCCC discoveries to clinical and community interventions aligned with the needs of New Mexico.

Strategic engagement with the other UNMCCC Research Programs, CWGs, and CPDM amplifies the translation of the CT Program's discoveries into interventional trials. Ongoing collaborations with CMO and CCPS are sustained by prioritizing the integration of correlative studies in clinical protocols to validate mechanisms of action and identify predictive biomarkers of response. Major accomplishments include the successful translation to multi-site, first-in-human, phase I/II trials that have subsequently advanced to national phase II trials [Funding: NCT04130516, NCT06624644, and NRG-GY021; NCT04034927; Prossnitz and Adams). Three new multi-site interventional IITs testing novel prevention and treatment strategies for endometrial cancer have also been opened through the Route66 SPORE (Funding: NCIP50CA265793, Leslie, MPI).

Research Accomplishments and Scientific Highlights:

• Targeted therapeutics (also Aim 1 and 2)
• Discovery of GPER/ER-selective ligands and advancement to phase II/III trials (also Aims 1 and 2)
• Combination immune therapy for ovarian cancer evaluated in two national trials (also Aim 2)
• Development of a multi-site therapeutic IIT for leukemia
• NCORP leadership enhances UNMCCC IITs to address catchment needs in breast cancer diagnosis and treatment